Vaccines capable of inducing protective antitumor immunity are urgently needed. Plasmid DNA (pDNA) vaccination represents an appealing strategy because it can elicit T cell responses, an essential component of antitumor immunity, and because several antigens can be included in a single vaccine, thus minimizing the risk of tumor escape. Also, pDNA is economical, easy to produce and standardize, and should induce few, if any, side effects. Under SBIR Phase I, a new pDNA cancer vaccine procedure will be explored for feasibility. T cell responses and protection against tumor challenge will be assessed in mice immunized using plasmids containing murine melanoma CTL epitopes. Vaccination will use the intra lymph node route, which is known as very efficient. Vaccine will be delivered by electroporation, a delivery method that increases magnitude, duration and distribution of gene expression. Strength and duration of antigenic stimulus in secondary lymphoid organs is a main determinant of priming efficacy of T cell responses. To maximize response, boosting regimes and genetic adjuvants will be tested. Under SBIR Phase II, studies will include procedure assessment in mice transgenic for human tumor antigens, development of a delivery device suitable for clinical use and initiation of a Phase I clinical trial